Abstract 559: Augmented Urinary Angiotensinogen in Young Type-1 Diabetic Subjects Correlates with Hemoglobin A1c and Urinary 8-Isoprostane

Abstract

Previous studies indicate that the intrarenal renin-angiotensin system (RAS) is activated in type-1 diabetes mellitus (T1DM) experimental animal models and human subjects, and is reflected by augmentation of urinary angiotensinogen (uAGT) excretion rate. Studies were performed to evaluate uAGT in young patients with short duration diabetes mellitus (DM) and its relationships with HbA1c and urinary 8-isoprostane excretion rate. Blood and urine samples were collected from 77 young (15±1 years) patients (44 male, 33 female) with short duration T1DM treated only with insulin and 36 (17 male, 19 female) control subjects. Serum glucose levels were 85±4 mg/dl in control subjects and 192±11 mg/dl in DM patients. Urinary Alb/Cr and uPro/Cr ratios were not significantly different in DM patients compared to control (8.6±.9 vs 9.7±.6 and 51±8 vs 62±14 mg/g). However, the uAGT/Cr ratios were significantly elevated in the DM patients (6.8±.8 vs 16.5±1.5 ug/g). Correlation analysis demonstrated highly significant relationships (P<.0001) between uAGT/Cr and HbA1c (R=.44) and urinary 8-isoprostane excretion rate (R=.52) in the DM patients. These results indicate that, even in young non-albuminuric patients with relatively short duration of DM, uAGT excretion rates are increased, suggesting early activation of the intrarenal RAS, and are correlated with HbA1c and urinary 8-isoprostane levels indicative of increased reactive oxygen species. Accordingly, uAGT levels may serve as an early marker of an activated intrarenal RAS and provide a specific index of renal RAS status potentially useful in monitoring clinical response to therapy.